MECHANISM OF LIPID-PEROXIDATION IN CANCER-CELLS IN RESPONSE TO GAMMA-LINOLENIC ACID (GLA) ANALYZED BY GC-MS .1. CONJUGATED DIENES WITH PEROXYL (OR HYDROPEROXYL) GROUPS AND CELL-KILLING EFFECTS
S. Takeda et al., MECHANISM OF LIPID-PEROXIDATION IN CANCER-CELLS IN RESPONSE TO GAMMA-LINOLENIC ACID (GLA) ANALYZED BY GC-MS .1. CONJUGATED DIENES WITH PEROXYL (OR HYDROPEROXYL) GROUPS AND CELL-KILLING EFFECTS, Anticancer research, 13(1), 1993, pp. 193-200
We have investigated the nature of lipid peroxidation occurring in ass
ociation with cancer-killing produced by gamma-linolenic acid (GLA) an
d iron (Fe) in cultured human breast cancer cells (ZR-75-1: ZR). UV-sp
ectrophotometry, high performance liquid chromatography (HPLC) and gas
chromatography (GC) or gas chromatography-mass spectrometry (GC-MS) h
ave been used to analyze lipid peroxides and their derivatives. Format
ion of conjugated dienes (CD), the conversion of triphenylphosphine (T
PP) to its oxide (TPPO), and the simultaneous production of hydroxy po
lyunsaturated fatty acids (PUFA-OHs) from these corresponding PUFAs hy
droperoxides (PUFA-OOHs) were analyzed in the total lipid extract -of
ZR cells and of normal human skin fibroblasts (CCD-41Sk:Sk). Fe enhanc
ed the formation of both the CD and TPPO and increased the percentage
of dead cells, while vitamin E inhibited these effects. Neither of the
se events was observed al any significant level in Sk cells. Identity
of PUFA-OHs was confirmed by determining the regional positions of the
hydroxyl group by GC-MS analysis of hydrogenated methyl ester tert-bu
tyldimethylsilyl ether alcohol derivatives (Me-H2-PUFA-O-TBDMS). The r
egional isomers identified were 15-, 12-and 8-OH 20 carbon and 13-OH 1
8 carbon fatty acid derivatives. These results suggest that the increa
sed formation of conjugated dienes and/or hydroperoxyl (or peroxyl) gr
oups in PUFA molecules is relevant to the cancer cell-killing effect o
f GLA + Fe.